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- All Subjects: Immunology
- Creators: School of Life Sciences
- Member of: Theses and Dissertations
Moraxella catarrhalis is a gram negative commensal bacteria that is a primary cause of otitis media in infants and severe exacerbations of COPD in adults. M. catarrhalis treatment has become increasingly difficult and expensive over the past half-century due to the emergence of beta-lactamase producing strains. There are currently no vaccines available to protect against infections. In this paper, we propose a transcriptomics-based approach for identifying potential vaccine targets. Additionally, a novel method was used to create bacterial vaccine polypeptides composed of sequence conserved peptides secreted through the outer membrane. Polypeptides were tested for immunogenicity and protective capacity in mice. We show that relative abundance of outer membrane proteins does not correlate with immunogenicity. We also show promising results for polypeptide protection in a mouse pulmonary clearance model.
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,
the VDR/RXR dimer binds 1,25(OH)2D3 to cause skin-specific effector T cell migration.
Targeted migration is a potent addition to current vaccines, as it would induce activated T cell
trafficking to appropriate areas of the immune system and ensure optimal stimulation (40).
ATRA, while in use clinically, is limited by toxicity and chemical instability. Rexinoids
are stable, synthetically developed ligands specific for the RXR. We have previously shown that
select rexinoids can enhance upregulation of gut tropic CCR9 receptors on effector T cells.
However, it is important to establish whether these cells can actually migrate, to show the
potential of rexinoids as vaccine adjuvants that can cause gut specific T cell migration.
Additionally, since the RXR is a major contributor to VDR-mediated transcription and
epidermotropism (15), it is worth investigating whether these compounds can also function as
adjuvants that promote migration by increasing expression of skin tropic CCR10 receptors on T
cells.
Prior experiments have demonstrated that select rexinoids can induce gut tropic migration
of CD8+ T cells in an in vitro assay and are comparable in effectiveness to ATRA (7). The effect
of rexinoids on CD4+ T cells is unknown however, so the aim of this project was to determine if
rexinoids can cause gut tropic migration in CD4+ T cells to a similar extent. A secondary aim
was to investigate whether varying concentrations in 1,25-Dihydroxyvitamin D3 can be linked to
increasing CCR10 upregulation on Jurkat CD4+ T cells, with the future aim to combine 1,25
Dihydroxyvitamin D3 with rexinoids.
These hypotheses were tested using murine splenocytes for the migration experiment, and
human Jurkat CD4+ T cells for the vitamin D experiment. Migration was assessed using a
Transwell chemotaxis assay. Our findings support the potential of rexinoids as compounds
capable of causing gut-tropic migration in murine CD4+ T cells in vitro, like ATRA. We did not
observe conclusive evidence that vitamin D3 causes upregulated CCR10 expression, but this
experiment must be repeated with a human primary T cell line.